Coarse-grained simulations uncover Gram-negative bacterial defense against polymyxins by the outer membrane.

ABSTRACT: The outer membrane (OM) of Gram-negative bacteria is a formidable barrier against antibiotics. Understanding the structure and function of the OM is essential for the discovery of novel membrane-acting agents against multidrug-resistant Gram-negative pathogens. However, it remains challenging to obtain three-dimensional structure of bacterial membranes using crystallographic approaches, which has significantly hindered the elucidation of its interaction with antibiotics. Here, we developed an asymmetric OM model consisting of rough lipopolysaccharide (LPS) and three key types of phospholipids. Using coarse-grained molecular dynamics simulations, we investigated the interaction dynamics of LPS-containing OM with the polymyxins, a last-line class of antibiotics against Gram-negative 'superbu

SUBMITTER: Jiang X 

PROVIDER: S-EPMC8441625 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature